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The Structure−Activity Relationship of the Antimalarial Ozonide Arterolane (OZ277) | Journal of Medicinal Chemistry
    Article

    The Structure−Activity Relationship of the Antimalarial Ozonide Arterolane (OZ277)
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    College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE
    Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
    § Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia
    Basilea Pharmaceutica Ltd., Grenzacherstrasse 487, CH-4058 Basel, Switzerland
    F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
    *To whom correspondence should be addressed. E-mail: [email protected]. Tel: 402-559-5362. Fax: 402-559-9543.
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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2010, 53, 1, 481–491
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    https://doi.org/10.1021/jm901473s
    Published November 19, 2009
    Copyright © 2009 American Chemical Society

    Abstract

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    The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.

    Copyright © 2009 American Chemical Society

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    Elemental analysis and HRMS data for 1, 6, and 1543. This material is available free of charge via the Internet at http://pubs.acs.org.

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    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2010, 53, 1, 481–491
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    https://doi.org/10.1021/jm901473s
    Published November 19, 2009
    Copyright © 2009 American Chemical Society

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